[Possible spoiler speculation for Harry Potter and the Revenge of the Sith]
Lance Mannion speculates a bit as to who's going to die in the final Harry Potter book; so too, the other day, did Steven Den Beste. (Scroll down to the 8-1-06 entries; SDB eschews permalinks on his current blogging platform.) SDB's guesses (Lupin and Snape) are definitely two characters who might die, but I'm not sure they're both what are referred to in the news as "major". Snape is certainly a major character, no doubt about it, but I don't think Lupin is. He's more of a supporting character.
Of course, that doesn't mean that Lupin won't die. Rowling is on record talking about major characters dying, and I frankly imagine that the final book will leave quite a few supporting players as portraits in the halls of Hogwarts. Frankly, I'd be surprised if someone known fairly well didn't die by Chapter Three. This is going to be the "all the marbles" book, and I strongly suspect that Rowling's going to up the ante very early on.
Lance thinks about it a bit, and concludes that Hagrid and Neville Longbottom will be the ones. Again, maybe half-right: Hagrid could go, and Neville could use the kind of hero's death that Lance talks about. But again, I'm not sure how major a character Neville is. I can't decide if he's a supporting character or a major one, really. So maybe he dies, maybe not. I confess that I've never really seen Hagrid as "doomed", but if he is doomed, I think that he would be more likely for the kind of hero's death that Lance speculates for Neville: in that one moment, Hagrid will finally be able to wield some kind of magical power and strike one great blow against Voldemort before expiring. Neville, to be honest, seems to me likely to survive and become one of the next great teachers at Hogwarts -- maybe a Professor McGonagall for the next generation.
So who do I think is most likely to die? Well, I'm prone to splitting the difference between Lance and SDB, and go with Hagrid and Snape. I can't see Snape really surviving, as Lance suggests, to serve as a kind of Obi Wan figure for Harry in his adulthood, because Harry's already had an Obi Wan figure in Dumbledore. I'll also say this: the movies of the last two books will probably finally allow Alan Rickman the chance to supplant Hans Gruber as his most successful portrayal of villainy.
Finally, on a non-death speculation note, it seems to me that there is some part still to be played by those most annoying of London suburb dwellers, the Dursleys. With the way nearly everything in Rowling's tale seems to play a part in some way, I can't believe she would have kept the Dursleys around this long if they were just comic relief for the first couple of chapters each time out. What could that role be? I don't know. One idea I rather like is that one of Voldemort's horcruxes turns out to be some hideous knick-knack on the Dursleys' mantelpiece, but I'm just making that up off the top of my head.